Discover. Oncology最新文献

{"title":"Targeting inflammatory pathways in hepatocellular carcinoma: recent developments.","authors":"Fulufhelo Tabitha Ramaite, Sanah Malomile Nkadimeng","doi":"10.1007/s12672-025-03035-8","DOIUrl":"10.1007/s12672-025-03035-8","url":null,"abstract":"<p><p>Chronic inflammation is a well-established driver of malignancy in many various cancer conditions. Hepatocellular carcinoma (HCC) is a significant illustrator of cancer linked to an inflammatory response and known to arises from prolonged liver damage. Inflammation is ranked number five of the most common factors in the occurrence of cancer conditions globally. Furthermore, it is placed third as the leading reason for cancer-related deaths, accompanied by nearly a million new diagnosis and fatalities annually. Pathological inflammation causes an ongoing liver damage and regeneration, which leads to fibrosis, cirrhosis, and eventually HCC. Although various factors contribute to HCC, a common mechanism is the inflammatory response that is triggered by cell death and the resulting inflammatory cascades. This review assesses recent progress in liver cancer research, focusing on how inflammatory pathways contribute to disease progression. It highlights the role of cytokines along with other inflammatory mediators in the progression of HCC stemming from chronic liver damage. The review also explores new therapeutic approaches targeting inflammatory pathways, including novel compounds and synthetic agents, such as IL-6 receptor antagonist and NF-κB pathway blockers and their potential for effectively treating and preventing liver cancer. Furthermore, it addresses current limitations and challenges in targeting inflammatory signalling and outlines future research directions to advance the clinical development of anti-inflammatory agents for liver cancer prevention and treatment.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1174"},"PeriodicalIF":2.8,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA- 103 as a novel potential biomarker of poor prognosis and durg resistance in solid tumours.","authors":"Xiaoping Xia, Xiuping Weng, Tianyu Liang, Mingxia Xu, Chao Zhang","doi":"10.1007/s12672-025-02963-9","DOIUrl":"10.1007/s12672-025-02963-9","url":null,"abstract":"<p><strong>Backgroud: </strong>Multiple studies have reported that microRNA-103 is unregulated in a variety of tumours, involved in tumorigenesis, and associated with tumour prognosis, so a systematic review and meta-analysis were performed to determine the relationship between microRNA-103 and the prognosis of solid tumours.</p><p><strong>Methods: </strong>The PubMed, Web of Science, and EMBASE databases were searched to retrieve articles to determine the relationship between microRNA-103 and tumour prognosis. Relevant articles were graded according to the Newcastle-Ottawa Scale (NOS). The 95% confidence interval (CI) was calculated by the fixed-effect/random-effect models and the risk ratio (RR) were summarised.</p><p><strong>Results: </strong>Eight out of 162 retrieved articles were included in this review, with an average NOS score of 7.2 points. Four studies of tissue samples and four studies of serum samples suggested that the overexpression of microRNA-103 was associated with overall survival (RR = 2.65, 95% CI: 1.79-3.93, P = 0.000 and RR = 3.31, 95% CI: 2.04-5.36, P = 0.000, respectively).</p><p><strong>Conclusion: </strong>This meta-analysis, combining 9 studies, found that overexpression of miRNA-103 is associated with poor prognosis in solid tumours, particularly in serum samples. Sensitivity analysis confirmed that high tissue expression correlates with poor outcomes. miRNA-103's role in tumor progression suggests its potential as a prognostic biomarker for solid tumors, warranting further research for clinical applications.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1177"},"PeriodicalIF":2.8,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the causal relationship between CX3CL1 and prostate cancer prognosis using Mendelian randomization.","authors":"Weisheng Li, Baoguo Xia, Weixin Chu, Likui Lu, Xuedong Liu","doi":"10.1007/s12672-025-03001-4","DOIUrl":"10.1007/s12672-025-03001-4","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is a common cancer in men, making up about 21% of male cancer cases worldwide. Although prostate cancer is common, little is known about its causes, which makes treatment more difficult. Studies suggest that immunity and inflammation are linked to prostate cancer. This study explores whether inflammatory mediators play a role in its development and outcome.</p><p><strong>Methods: </strong>Single-nucleotide polymorphisms (SNPs) associated with CX3CL1 expression (GWAS ID: ebi-a-GCST90012074) were identified from a genome-wide association study (GWAS) of 21,758 individuals of European descent. Summary-level data from three PCa GWAS datasets were obtained from the UK Biobank: ieu-b-4809 (9,132 cases and 173,493 controls), ukb-b-1392 (7,847 cases and 455,163 controls), and ukb-d-C3_PROSTATE (6,321 cases and 354,873 controls). Mendelian randomization (MR) was first used to assess the causal relationship between CX3CL1 and PCa. A meta-analysis was then conducted to evaluate the overall genetically predicted risk. Finally, the impact of CX3CL1 on PCa was further explored using gene expression data, immune cell infiltration profiles, survival analysis, and single-cell sequencing.</p><p><strong>Results: </strong>Two-sample Mendelian randomization analysis indicated that CX3CL1 was inversely associated with PCa risk. The subsequent meta-analysis supported a consistent inverse causal relationship between CX3CL1 levels and PCa risk. Further analysis showed that CX3CL1 expression was significantly downregulated in tumor tissues compared with normal tissues, and was positively correlated with immune cell infiltration. Lower CX3CL1 expression was also associated with poorer prognosis in PCa patients. In addition, single-cell sequencing revealed that CX3CL1 expression was markedly reduced in cancer cells compared with other cell populations within the tumor microenvironment.</p><p><strong>Conclusion: </strong>This study demonstrated that genetically predicted CX3CL1 levels are inversely associated with PCa risk. Further analysis using public databases showed that reduced CX3CL1 expression in PCa cells is associated with lower immune cell infiltration, which may contribute to poorer prognosis. These findings suggest that CX3CL1 may serve as a potential biomarker for predicting PCa risk and patient outcomes and that immunotherapy strategies targeting CX3CL1 could offer therapeutic benefits for PCa patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1175"},"PeriodicalIF":2.8,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of survival-dependent genes in esophageal cancer via the DepMap database: unraveling their association with immune infiltration.","authors":"Xiangrong Yao, Junyan He, Wentao Xiao, Limou Chen, Fangzhu Xiao","doi":"10.1007/s12672-025-02942-0","DOIUrl":"10.1007/s12672-025-02942-0","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer ranks as the 11th most diagnosed cancer worldwide and the 7th leading cause of cancer-related deaths, mainly due to late-stage diagnosis. Identifying novel biomarkers is essential for enhancing prognostic evaluations and targeting patients for immunotherapy.</p><p><strong>Methods: </strong>We used the DepMap database to identify survival-dependent genes in esophageal carcinoma cells. A prognostic model was developed using univariate and multivariate Cox regression and LASSO, validated with the GEO dataset. WGCNA and GSEA analyses were conducted to explore mechanisms, alongside ESTIMATE and ssGSEA for prognosis.</p><p><strong>Results: </strong>We constructed a novel four-gene prognostic signature (CPSF6, IGBP1, MTG2, TCP1) based on SDG expression and survival data. This signature stratified esophageal cancer patients into high- and low-risk groups with significantly different survival, with the high-risk group showing shorter survival. WGCNA and GSEA analyses linked prognosis to immune pathways, including interferon-γ response and IL6-JAK-STAT3 signaling. ssGSEA revealed reduced infiltration of 19 immune cell types in high-risk patients, and ESTIMATE analysis confirmed the association between immune infiltration and poor prognosis.</p><p><strong>Conclusion: </strong>This study establishes a four-gene survival signature for esophageal cancer that distinguishes high-risk from low-risk populations, providing novel prognostic indicators. Immune response pathways were downregulated in high-risk patients, offering potential targets for understanding esophageal cancer mechanisms and developing immunotherapeutic strategies.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1176"},"PeriodicalIF":2.8,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cutting-edge dynamics and research hotspots on boswellic acid in cancer: a bibliometrics analysis from 1994 to 2024.","authors":"Minghe Lv, Lei Tang, Yue Feng, Su Zeng, Hongwei Zeng, Jingping Yu, Qing Ji, Ruping Zhao","doi":"10.1007/s12672-025-02953-x","DOIUrl":"10.1007/s12672-025-02953-x","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have highlighted the potential of boswellic acid as a promising therapeutic option in cancer treatment. Despite its growing relevance, there has been a lack of bibliometric analysis exploring the relationship between boswellic acid and cancer. The primary objective of this study was to provide a comprehensive overview of the research landscape, knowledge structure, and emerging trends surrounding boswellic acid and its potential use in oncology.</p><p><strong>Method: </strong>We conducted a search in the Web of Science Core Collection (WoSCC) database for publications related to boswellic acid and cancer from 1994 to 2024. Bibliometric analysis was performed using tools such as VOSviewer, CiteSpace, and the R package \"bibliometrix\" to visualize and interpret the data.</p><p><strong>Results: </strong>The analysis included 332 publications from 49 different countries, with India and China leading in research output. The number of annual publications on boswellic acid and cancer has steadily increased since 2015. The University of Nizwa was identified as the leading institution contributing to this field. The European Journal of Medicinal Chemistry emerged as the most popular journal for publishing articles on this topic, while Planta Medica and Cancer Research received the highest citation counts. The author with the highest number of publications was Al-Harrasi Ahmed, and the most frequently co-cited researcher was Jian-Jun Liu. Emerging research hotspots include key terms such as \"phytochemicals\", \"pharmacokinetics\", and \"bioavailability\".</p><p><strong>Conclusion: </strong>This bibliometric analysis provides valuable insights into the current state of research on boswellic acid in cancer treatment. It serves as a useful resource for researchers and scholars seeking to explore the evolving landscape of boswellic acid's role in oncology, highlighting that \"phytochemicals\", \"pharmacokinetics\", and \"bioavailability\" might be the key research directions and trends of boswellic acid in cancer research.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1173"},"PeriodicalIF":2.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotechnology in oncology: advances in biosynthesis, drug delivery, and theranostics.","authors":"Mohamed M Ammar, Rania Ali, Naira Ali Abd Elaziz, Heba Habib, Fatima M Abbas, Mohamed Taha Yassin, Khalid Maniah, Rewan Abdelaziz","doi":"10.1007/s12672-025-02664-3","DOIUrl":"10.1007/s12672-025-02664-3","url":null,"abstract":"<p><p>Nanotechnology has revolutionized oncology by offering innovative solutions to overcome the limitations of conventional cancer therapies. This review explores the transformative potential of nanotechnology in cancer diagnosis, treatment, and drug delivery, emphasizing the development of sustainable nanocomposites derived from natural sources such as plants and microbes. These eco-friendly nanocomposites enhance therapeutic efficacy, minimize environmental impact, and align with green chemistry principles. Nanoparticles (NPs) enable targeted drug delivery through mechanisms like the enhanced permeability and retention (EPR) effect and active targeting, reducing systemic toxicity and improving treatment outcomes. They also facilitate gene therapy, photothermal and photodynamic therapies, and immune modulation, including the development of cancer vaccines and theranostic platforms. Despite their promise, challenges such as nanoparticle toxicity, immune clearance, and long-term biocompatibility persist. Advances in biodegradable and stimuli-responsive NPs aim to address these issues, ensuring safer and more effective applications. The integration of nanotechnology with personalized medicine and combination therapies holds significant potential for improving cancer treatment efficacy and patient outcomes. However, further research is needed to optimize nanoparticle design, enhance tumor targeting, and ensure clinical translation. This review highlights the critical role of nanotechnology in advancing cancer therapy, underscoring its potential to redefine treatment paradigms while addressing current limitations and future prospects.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1172"},"PeriodicalIF":2.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global research trends on Chinese patent drugs inducing programmed cell death in cancer: a bibliometric analysis (1998-2024).","authors":"Min Song, Chunyan Teng, Xiaodong Zheng, Shizhen Tan, Yipeng Guo","doi":"10.1007/s12672-025-02913-5","DOIUrl":"10.1007/s12672-025-02913-5","url":null,"abstract":"<p><strong>Background: </strong>Chinese patent drugs, standardized formulations rooted in traditional Chinese medicine, have gained attention for their potential to induce programmed cell death (PCD) in cancer cells. Emerging evidence suggests that these formulations may affect multiple PCD pathways, including apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis, thus offering a multifaceted approach to tumor suppression.</p><p><strong>Objectives: </strong>This study aimed to map the global research landscape on Chinese patent drugs in cancer-related PCD, examining publication trends, principal contributors, and thematic evolutions. The analysis also sought to provide insights that could guide future investigations and clinical applications.</p><p><strong>Methods: </strong>Bibliometric data were extracted from the Web of Science Core Collection (1998-2023), focusing on articles investigating Chinese patent drugs and PCD in oncological contexts. R-bibliometrix was used for descriptive statistics and trend analyses, while VOSviewer generated network visualizations of co-occurring keywords, collaboration patterns, and co-citation clusters.</p><p><strong>Results: </strong>Overall publication output increased markedly, with China leading in both volume and impact. Collaboration networks revealed extensive international partnerships, underscoring global interest in standardized herbal formulations. Keyword mapping highlighted a shift from early apoptosis-centric studies to more diverse regulated cell-death pathways, indicating greater mechanistic depth and exploration of synergistic effects with conventional therapies.</p><p><strong>Conclusion: </strong>Chinese patent drugs are increasingly recognized as promising agents for modulating PCD in cancer cells. Ongoing work focuses on standardized manufacturing, robust clinical validation, and mechanistic elucidation. These trends position Chinese patent drugs at a pivotal juncture for advancing integrative oncology and enhancing patient outcomes.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1171"},"PeriodicalIF":2.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAM64A silencing inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition in ovarian cancer cells via activating Hippo pathway.","authors":"Jianxiu Luo, Ruiyang Li","doi":"10.1007/s12672-025-02710-0","DOIUrl":"10.1007/s12672-025-02710-0","url":null,"abstract":"<p><strong>Objective: </strong>Ovarian cancer (OC) is a highly aggressive malignancy in females. We aim to investigate the potential gene target and examine its impact on OC.</p><p><strong>Methods: </strong>Hub genes were determined using protein-protein interaction networks based on differently expressed genes in GSE12470 and GSE14407 datasets. The impact of FAM64A on the malignant phenotype of OC cells was evaluated by cell counting kit-8, 5-ethynyl-2'-deoxyuridine staining, wound healing, and transwell assays. The epithelial-mesenchymal transition (EMT) process was assessed by determining the protein expression of E-cadherin, N-cadherin, and Vimentin.</p><p><strong>Results: </strong>We identified the 18 hub genes of OC with substantial predictive value. FAM64A was selected as a candidate gene. The silencing of FAM64A suppressed the viability (si-NC: 0.78 ± 0.04, 0.95 ± 0.08; si-FAM64A: 0.58 ± 0.05, 0.64 ± 0.11), proliferation (si-NC: 100.00 ± 9.36, 100.00 ± 14.70; si-FAM64A: 34.79 ± 8.88, 44.55 ± 4.91), migration (si-NC: 61.92 ± 8.06, 60.08 ± 5.22; si-FAM64A: 45.88 ± 8.36, 37.78 ± 7.29), and invasion (si-NC: 130.00 ± 10.34, 144.00 ± 13.40; si-FAM64A: 81.00 ± 16.99, 115.60 ± 13.30) of A2780 and SKOV3 cells. FAM64A silencing reduced the EMT in OC cells. The Hippo pathway was identified as the central pathway implicated in the regulatory role of FAM64A in OC. The silencing of FAM64A caused an increase in the protein expression within the Hippo pathway in both A2780 and SKOV3 cells.</p><p><strong>Conclusion: </strong>Knockdown of FAM64A emerges as a promising therapeutic target for OC, exerting an inhibitory role in OC by activating the Hippo pathway.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1160"},"PeriodicalIF":2.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating multi-omics data to optimize immunotherapy in endometrial cancer: a comprehensive study.","authors":"Xin Guan, Rongchuan Cao, Longbi Liu, Lin Ma, Ning Gao, Yanfei Yang, Mingyue Xiao, Rui Du, Yuzhe Su, Zhen Wang, Xiaofeng Liu, Lu Han","doi":"10.1007/s12672-025-02978-2","DOIUrl":"10.1007/s12672-025-02978-2","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Immunotherapy represents a pivotal therapeutic modality in endometrial cancer (EC). Nevertheless, the efficacy of this treatment is limited to a subset of patients. The present investigation endeavors to amalgamate multi-omics data in order to elucidate the determinants impacting individual immune responsiveness and enhance the optimization of immunotherapy for EC. To differentiate EC patients into non-response (NR) and response (R), multi-omics data from publicly available databases were employed in conjunction with the TIDE computational framework. The validity of these findings was further confirmed through the utilization of the EaSIeR and ImmunoPhenoScore algorithms. The study employed functional enrichment and gene set variant analysis to discern noteworthy disparities in biological pathways across various groups. Moreover, three deconvolution algorithms (ESTIMATE, TIMER, and EPIC) were employed to quantify the tumor microenvironment (TME). Somatic mutation and copy number variant (CNV) analyses were also conducted to identify genomic alterations that impact immunotherapy. Integrated bulk and single-cell RNA sequencing (scRNA-seq) data were employed to identify cell populations linked to efficacy and deduce cell-cell interactions. The immunotherapy response rates were found to be greater in elderly EC patients aged 65 years and above. The NR group of patients displayed notable enrichment in cellular differentiation, angiogenesis, and tumor proliferation characteristics, as evidenced by higher tumor purity and lower expression of immune checkpoints. Conversely, the R group exhibited a stronger correlation with immunity, as indicated by pathway enrichment and composition of TME. Patients in the NR group demonstrated higher frequencies of somatic mutations, with a 2- to 6-fold disparity between the groups in genes such as RPRD1B and CTNNB1. Patients in the R group exhibited elevated mutation scores and higher mutation frequencies at the same mutation loci compared to those in the NR group. Moreover, the incidence of mutations was more prevalent among patients in the R group. In independent cohorts, the Scissor algorithm suggests that macrophages may exert a substantial impact on immunotherapy response in patients with EC. Subsequent analysis unveiled an enrichment of M2-like tumor-associated macrophages (TAMs) within the TME of patients in the NR group. These macrophages facilitate angiogenesis and cell proliferation through intercellular communication with subpopulations such as endothelial and epithelial cells. TME of patients in the R group exhibited an enrichment of M1-like TAMs, which primarily engaged with immune cells via diverse immune-activating factors. Furthermore, immunohistochemistry and flow cytometry demonstrated that responders to immunotherapy had significantly increased infiltration of M1-like TAMs. M1-like TAMs were shown to inhibit proliferation and migration of Ishikawa cells in co-culture assays. This research offer","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1161"},"PeriodicalIF":2.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect and mechanism of PYCR1 on biological function of hepatocellular carcinoma cells under hypoxia.","authors":"Jiayi Guo, Xinxin Jin, Junli Zhang, Yuming Zhang, Wenjuan Wu","doi":"10.1007/s12672-025-03028-7","DOIUrl":"10.1007/s12672-025-03028-7","url":null,"abstract":"<p><strong>Background: </strong>Pyrrole-5-carboxylate reductase 1 (PYCR1) is a key enzyme involved in proline synthesis, which is closely related to the occurrence and development of liver cancer. In this study, we aimed to investigate the relationship and mechanism of PYCR1 on proline metabolism in hepatocellular carcinoma cells under hypoxic conditions.</p><p><strong>Methods: </strong>GO and KEGG enrichment analyses were used to predict the biological function and possible mechanism of PYCR1 in hypoxic microenvironments. The energy metabolism kit and Western blot were used to detect the metabolic changes of SUN449 and Hep3B liver cancer cells under hypoxic conditions. The proliferative capacity of cells was evaluated using EDU incorporation assay and the Ki67 staining protocol. The apoptotic rates and Western blot were measured using flow cytometry. Additionally, Western blot analysis was used to examine the levels of proteins associated with relevant signaling pathways and pathway inhibitors.</p><p><strong>Results: </strong>GO enrichment analysis showed that hypoxic PYCR1 might be related to amino acid metabolism. The 1% hypoxia model promoted proline synthesis and lactate dehydrogenase synthesis in hepatocellular carcinoma cells. Knockdown of PYCR1 reverses hypoxia-induced proline synthesis and NAD⁺/NADH ratio. PYCR1 promoted the proliferation of hepatocellular carcinoma cells under hypoxic conditions. PYCR1 knockdown reduces proliferation and increases apoptosis. Hypoxia can activate the MAPK/ERK/STAT3 pathway; knockdown of PYCR1 can inhibit the levels of ERK and STAT3 phosphorylated proteins, inhibit the proliferation of hepatocellular carcinoma cells, and the ERK inhibitor U0126 inhibits the expression of P-STAT3 in the downstream.</p><p><strong>Conclusion: </strong>In summary, we report that hypoxia-mediated PYCR1 promotes proline synthesis in HCC, cell proliferation, inhibits apoptosis, and ultimately promotes tumor progression through the MAPK/ERK/STAT3 signaling pathway, suggesting that PYCR1 is a potential therapeutic target for HCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1167"},"PeriodicalIF":2.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}